4,4'-Methylenedianiline, oligomeric reaction products with 1-chloro-2,3-epoxypropane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.5 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEC

Value:

87.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

The sub-chronic oral toxicity study is considered to be best suited to extrapolate to effects on the inhalation route.

AF for dose response relationship:

1

AF for differences in duration of exposure:

2

AF for interspecies differences (allometric scaling):

4

AF for other interspecies differences:

2.5

AF for intraspecies differences:

5

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The sub-chronic oral toxicity study is considered to be best suited to extrapolate to effects on the dermal route.

AF for dose response relationship:

1

AF for differences in duration of exposure:

2

AF for interspecies differences (allometric scaling):

4

AF for other interspecies differences:

2.5

AF for intraspecies differences:

5

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

DNEL related information

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

According to REACH "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishement of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, acute DNELs should default the long-term systemic DNELs.

For local effects, a DNEL was not quantifiable; However, as the substance is known to be a skin sensitizer, local effects must be assessed qualitatively and risk management measures applied as necessary. The potential for respiratory sensitization is unknown; however, given its skin sensitization potential, this endpoint should also be assessed qualitatively.

The dose descriptor starting point for DNEL calculation used:

NOAEL: 50 mg/kg bw (determined during an repeated dose oral toxicity study in rats performed in 2013).

By default the dermal absorption was considered to be 100%.

For inhalation, a NAEL human was determined using an allometric scaling of 4 and a body weight of 70 kg and found to be 12.50 mg/kg, resulting in a corrected NAEC human of 87.5 mg/m³.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)